机构地区:[1]金华市中心医院药学部,浙江金华321000 [2]杭州医学院药学系,浙江杭州310000
出 处:《中国临床药理学杂志》2021年第6期707-709,共3页The Chinese Journal of Clinical Pharmacology
摘 要:目的研究白藜芦醇对膜性肾病大鼠的肾保护作用及可能的作用机制。方法将SD大鼠随机分为正常组、模型组及实验组,各20只。用尾静脉注射阳离子化牛血清白蛋白(C-BSA)构建膜性肾病大鼠,正常组给予等量生理盐水。建模后实验组灌胃白藜芦醇(30 mg·kg-1),模型组及正常组灌胃等量生理盐水,每天1次,连续干预4周。用分光光度计检测24 h尿蛋白定量(UTP),用试剂盒检测血清中肌酸酐(Scr)、尿素氮(BUN)、白蛋白(ALB)、总胆固醇(TC)指标水平,以免疫组化法检测大鼠肾组织synaptopodin蛋白表达情况,以蛋白质印迹(WB)法检测大鼠肾组织中p-Akt、mTOR、PI3K蛋白表达。结果正常组、模型组和实验组大鼠血清中Scr分别为(29.16±1.77),(52.64±2.78)和(40.55±2.65)μmol·L^(-1),BUN分别为(5.86±1.35),(13.54±2.36)和(7.66±3.45)mmol·L^(-1),24 h UTP分别为(6.85±1.26),(39.52±1.24)和(25.36±1.42)mg,ALB分别为(32.15±3.49),(19.63±2.48)和(26.34±2.58)g·L^(-1),TC分别为(1.26±0.52),(4.02±0.36)和(2.36±0.52)mmol·L^(-1),肾组织synaptopodin蛋白表达量分别为(45.36±2.18)%,(12.63±3.85)%,(23.26±3.09)%,差异均有统计学意义(均P<0.05)。模型组肾组织中磷酸化蛋白激酶B(p-Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)、磷脂酰肌醇3-激酶(PI3K)相对表达量较正常组升高,而实验组低于模型组,差异均有统计学意义(均P<0.05)。结论白藜芦醇可减少膜性肾病大鼠尿蛋白程度,防止synaptopodin降解,降低PI3K/Akt/mTOR信号通路中蛋白表达,从而发挥对膜性肾病的肾保护作用。Objective To investigate the renal protective effect of resveratrol on rats with membranous nephropathy and its possible mechanism.Methods SD rats were randomly divided into normal group(n=20),model group(n=20)and test group(n=20).Rats with membranous nephropathy were established by injecting cationic bovine serum albumin(C-BSA)into tail vein.Normal group was given the same amount of normal saline.Test group was given 30 mg·kg-1 resveratrol by gavage,model group and normal group were given the same amount of normal saline by gavage once a day for 4 weeks.The urinary protein content(UTP)in 24 h was measured by spectrophotometer,serum creatinine(Scr),blood urea nitrogen(BUN),albumin(ALB)and total cholesterol(TC)were measured by kit.The expression of synaptopodin were detected by immunohistochemistry;and the expression of phosphorylated proten kinase B(p-Akt),mammalian target of rapmycin(m TOR)and phosphatidylinositol 3-kinase(PI3 K)were detected by Western blot(WB).Results Scr in the serum of normal group,model group and test group were(29.16±1.77),(52.64±2.78)and(40.55±2.65)μmol·L^(-1),BUN were(5.86±1.35),(13.54±2.36)and(7.66±3.45)mmol·L^(-1),24 h UTP were(6.85±1.26),(39.52±1.24)and(25.36±1.42)mg,ALB were(32.15±3.49),(19.63±2.48)and(26.34±2.58)g·L^(-1),TC were(1.26±0.52),(4.02±0.36)and(2.36±0.52)mmol·L^(-1),the expression of synaptopodin protein in kidney tissue were(45.36±2.18)%,(12.63±3.85)%and(23.26±3.09)%,all with significant difference(all P<0.05).The relative expression of p-Akt,m TOR,PI3 K in the kidney tissue of model group were higher than those in normal group,and those in test group were lower than those in model group,all with significant difference(all P<0.05).Conclusion Resveratrol can reduce the level of urine protein,prevent the degradation of synaptopodin,and decrease the protein expression in PI3 K/Akt/m TOR signaling pathway in rats with membranous nephropathy.
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